Clinical Trials /

Palbociclib and INCMGA00012 in People With Advanced Liposarcoma

NCT04438824

Description:

The researchers are doing this study to find out whether combining the study drugs palbociclib and INCMGA00012 is an effective and safe treatment for advanced liposarcoma.

Related Conditions:
  • Liposarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Palbociclib and INCMGA00012 in People With Advanced Liposarcoma
  • Official Title: A Phase II Study of CDK4/6 Inhibition (Palbociclib) Combined With PD-1 Blockade (INCMGA00012) in Patients With Advanced Well-differentiated and/or Dedifferentiated Liposarcoma

Clinical Trial IDs

  • ORG STUDY ID: 20-062
  • NCT ID: NCT04438824

Conditions

  • Well Differentiated Liposarcoma
  • Dedifferentiated Liposarcoma

Interventions

DrugSynonymsArms
INCMGA00012Palbociclib and INCMGA00012
PalbociclibPalbociclib and INCMGA00012

Purpose

The researchers are doing this study to find out whether combining the study drugs palbociclib and INCMGA00012 is an effective and safe treatment for advanced liposarcoma.

Trial Arms

NameTypeDescriptionInterventions
Palbociclib and INCMGA00012ExperimentalOne treatment cycle will consist of 28 days. Patients in both study phases will start palbociclib on Day 1 and INCMGA00012 on day 15 of each cycle at the following dose schedule: INCMGA00012: 500 mg IV (flat dose) q28 days Palbociclib: 125 mg PO daily for 21 days, followed by 7 days off, q28 days Palbociclib will be taken on Day 1 of each cycle for 21 consecutive days followed by 7 days off (days 22-28 of each Cycle). INCMGA00012 will be administered on Day 15 of each cycle and repeat every 28 days.
  • INCMGA00012
  • Palbociclib

Eligibility Criteria

        Inclusion Criteria:

          -  A diagnosis of metastatic or unresectable WD/DD liposarcoma. Unresectable is defined
             as if the primary tumor a) cannot be safely removed surgically or b) would benefit
             from systemic therapy prior to a surgical approach

          -  Measurable disease by RECIST 1.1

             a. Target lesions must not be chosen from a previously irradiated field unless there
             has been radiographically and/or pathologically documented tumor progression in that
             lesion prior to enrollment

          -  Age ≥ 18 years

          -  ECOG performance status 0 or 1

          -  Adequate organ and marrow function as defined below (ULN indicates institutional upper
             limit of normal):

               1. Absolute neutrophil count ≥ 1.5 x 109/L

               2. Hemoglobin ≥ 8.0 g/dL

               3. WBC ≥ 3.0 x 109/L

               4. Platelets ≥ 100 x 109/L

               5. ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels >
                  1.5 ULN. Except patients with Gilbert's disease (≤3x ULN)

               6. AST (SGOT) /ALT (SGPT) ≤ 3 x institutional ULN

               7. Creatinine Clearance > 50 mL/min (calculated by Cockcroft-Gault method)

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control or abstinence) during the trial period
             through at least 120 days after the last dose of study treatment.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Ability to swallow tablets

          -  Patients with brain metastasis that have been treated with definitive surgery or
             radiation, and have been clinically stable for 3 months are eligible

        Exclusion Criteria:

          -  Patients who have not recovered from clinically significant adverse events of prior
             therapy to ≤ NCI CTCAE v5 Grade 1, except alopecia and stable neuropathy, which must
             have resolved to Grade ≤ 2 or baseline.

          -  Patients receiving any other investigational agents.

          -  Patients who have received prior treatment with a selective CDK4 inhibitor or an
             anti-PD-1/PD-L1 agent

          -  Uncontrolled intercurrent illness including, but not limited to, known ongoing or
             active infection, including uncontrolled HIV, active hepatitis B or C, symptomatic
             congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmias,
             psychiatric illness/social situations that would limit compliance with study
             requirements, clinically significant interstitial lung disease or active noninfectious
             pneumonitis, or active infection requiring systemic therapy

               1. Patients with a CD4+ count of > 300 and an undetectable viral load who are
                  currently on HAART are eligible for inclusion

               2. Patients with NYHA class III or IV congestive heart failure within 6 months of
                  study treatment will be excluded

          -  Pregnant women and women who are breast-feeding.

          -  History or evidence of symptomatic autoimmune disease in past 2 years prior to
             enrollment.

             a. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or
             physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)
             is not considered a form of systemic treatment for autoimmune disease

          -  Prolonged QTcF > 450 ms for men and > 470 ms for women at Screening.

          -  Patients who have received a live vaccine within 30 days of the start date of the
             planned study therapy. Note: Seasonal influenza vaccines for injection are generally
             inactivated flu vaccines and are allowed; however intranasal influenza vaccines are
             live attenuated vaccines, and are not allowed

          -  Radiation therapy within 2 weeks prior to study Day 1

          -  Prior organ transplantation including allogenic stem-cell transplantation

          -  Known prior severe hypersensitivity to investigational product or any component in its
             formulations, including known severe hypersensitivity reactions to monoclonal
             antibodies (NCI CTCAE v 5 Grade ≥ 3)

          -  Patients who require concomitant use of medications that strongly induce or inhibit
             CYP3A (per section 15.0)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:confirm the recommended phase two dose (RP2D
Time Frame:within 6 weeks of treatment
Safety Issue:
Description:DLTs will be assess within the first 6 weeks of the treatment combination . DLT definitions are described in section 15.4, and will be defined using NCI CTCAE v 5.0. If ≤ 1 patient out of 6 has a dose-limiting toxicity, the dosing used in the safety lead-in phase will be declared the recommended phase 2 dose. If ≥ 2 of 6 patients in the safety lead-in experience a DLT, study treatment will be halted and no further patients will be enrolled. If the study is resumed with an alternative dosing schema, a new safety lead-in phase will be completed with the new dosing regimen

Secondary Outcome Measures

Measure:best overall response rate
Time Frame:48 weeks
Safety Issue:
Description:defined by RECIST v1.1

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Palbociclib
  • INCMGA00012
  • 20-062

Last Updated

June 18, 2020